The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier-wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop. As model drug carriers, fluorescent polymeric nanoparticles (FNPs) were chosen, which were obtained by using as starting material a pegylated polylactic acid-polyaspartamide copolymer. The latter was synthesized by derivatization of,-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) with Rhodamine (RhB), polylactic acid (PLA) and then poly(ethyleneglycol) (PEG) chains. It was found that the carrier concentration near the wall increases with increasing pressure drop, independently of RBC concentration, and that the tendency for FNP margination decreases with increasing hematocrit. This work highlights the importance of taking into account RBC-drug carrier interactions and physiological conditions in microcirculation when planning a drug delivery strategy based on systemically administered carriers.
|Numero di pagine||12|
|Stato di pubblicazione||Published - 2017|
All Science Journal Classification (ASJC) codes